This program project grant examines the interrelationships between vessel walls, endothelial cells, platelets, plasma coagulation proteins, lipoproteins, and antibodies in the process of thrombogenesis and atherogenesis. The first project examines the metabolism of endothelial cells, in particular the biosynthesis of collagen, factor VIII and lipids. The second project investigates the ability of collagen and other vessel wall macromolecules to activate Hageman factor, the first protein in the coagulation cascade in the presence of co-factors such as high molecular weight kininogen and prekallikrein. The third project deals with the synthesis, regeneration and composition of the platelet aggregating material shed by tumors and transformed cells. Project four concentrates on the role of low-density lipoprotein cholesterol in inducing platelet functional changes including hypersensitivity to aggregating agents, changes in membrane adenylate cyclase and microviscosity. The fifth project concerns the effects of heterologous and isologous antibodies on platelet structure and function. Studies will employ inhibitors of platelet aerobic and anaerobic metabolism and of prostaglandin synthesis as well as compounds effecting cyclic AMP metabolism. The final project is an in depth investigation of the biochemistry of bovine and human factor V including its subunit structure and interactions with phospholipids, calcium factor Xa and prothrombin. Many collaborative efforts between the investigators strengthen the possibilities of more fully understanding the mechanisms underlying thrombotic disorders.